Dioxin Case Control Study / Prof. Jean Francois Viel


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  • Dioxin Case Control Study / Prof. Jean Francois Viel

    1. 1. Dioxin emissions from a municipal solid waste incinerator and risk of non-Hodgkin lymphoma: a case-control study. Pr. Jean-François Viel, Faculty of Medicine, Besançon, France
    2. 2. Introduction <ul><li>1997 : the International Agency for Research on Cancer classifies the 2,3,7,8 TCDD as a human carcinogen. </li></ul><ul><li>1998 : the French Ministry of Environment reveals that dioxin concentration in exhaust gas from the MSWI of Besançon is 16.3 ng I-TEQ/m 3 . </li></ul><ul><li>2000 : o ur team finds evidence for clusters of non-Hodgkin lymphoma (SIR = 1.3) and soft-tissue sarcoma (SIR = 1.4) in the area that contains the MSWI : </li></ul><ul><ul><li>Viel JF, Arveux P, Baverel J , Cahn JY. Soft–tissue sarcoma and non-Hodgkin’s lymphoma clusters around a municipal solid waste incinerator with high dioxin emission levels. Am J Epidemiol 2000;152:13-19. </li></ul></ul>
    3. 3. Over-incidence SIR NHL : 1 . 3 (1 . 1-1 . 4) SIR ST S : 1 . 4 (1 . 1-1 . 9) : Besançon, Audeux : MSWI
    4. 4. Introduction (2) <ul><li>These results suggested an airborne route of dioxin exposure, which is at variance with the common assumption that intake from food accounts for over 90% of the burden of dioxins in the general human population. </li></ul><ul><li>This assumption may not hold for people living in the vicinity of a solid waste incinerator, however. </li></ul><ul><li>Possible exposure pathways include : </li></ul><ul><ul><li>direct exposure (vapor inhalation or dermal absorption), </li></ul></ul><ul><ul><li>more likely, the consumption of plant products or poultry from contaminated areas . </li></ul></ul>
    5. 5. Aim <ul><li>To compare the spatial distributions of cases and population-based controls: </li></ul><ul><ul><li>at the smallest level of geographic resolution, </li></ul></ul><ul><ul><li>according to their exposure to dioxins emitted by the MSWI, </li></ul></ul><ul><ul><li>while accounting for some confounding factors. </li></ul></ul>
    6. 6. The municipal solid waste incinerator of Besançon, France <ul><li>Began operation in 1971. </li></ul><ul><li>Located in an urbanized area. </li></ul><ul><li>Capacity: 7.2 metric tons/hour. </li></ul><ul><li>Stack: 40 m high. </li></ul><ul><li>Processing: 67,000 tons of waste (1998). </li></ul><ul><li>Emissions (1997): </li></ul><ul><ul><li>dioxin: 16.3 ng I-TEQ / m 3 , </li></ul></ul><ul><ul><li>dust: 315.6 mg / Nm 3 , </li></ul></ul><ul><ul><li>hydrogen chlorine: 803.5 mg / Nm 3 , </li></ul></ul><ul><ul><li>exhaust gases not maintained at temperatures ≥ 850°C for the legal time (> 2 s). </li></ul></ul>
    7. 7. Population and methods
    8. 8. Population (1) <ul><li>Study period: </li></ul><ul><ul><li>January 1, 1980 to December 31, 1995. </li></ul></ul><ul><li>Study area: </li></ul><ul><ul><li>City of Besançon (since detailed census data were available only for this area). </li></ul></ul><ul><li>Selection of cases: </li></ul><ul><ul><li>non-Hodgkin lymphoma incident cases, </li></ul></ul><ul><ul><li>living in Besançon at the time of diagnosis, </li></ul></ul><ul><ul><li>obtained from the local cancer registry. </li></ul></ul><ul><li>Selection of controls: </li></ul><ul><ul><li>randomly drawn from the population census database, </li></ul></ul><ul><ul><li>a t a bloc level , </li></ul></ul><ul><ul><li>matched for sex and age (5 age categories), </li></ul></ul><ul><ul><li>with a 10-to-1 procedure. </li></ul></ul>
    9. 9. Population (2) <ul><li>Block: </li></ul><ul><ul><li>the smallest level of geographic resolution, </li></ul></ul><ul><ul><li>defined only in densely populated areas, </li></ul></ul><ul><ul><li>typically a quadrangle bounded by four streets, </li></ul></ul><ul><ul><li>amounting to 705 blocks in Besançon, </li></ul></ul><ul><ul><li>averaging 161 inhabitants, </li></ul></ul><ul><ul><li>only 5 age categories (0-19, 20-39, 40-59, 60-74 and 75+ years) are available to researchers, because of French privacy laws. </li></ul></ul>
    10. 10. Population (3) <ul><li>Block group: </li></ul><ul><ul><li>the 705 blocks of the study area </li></ul></ul><ul><ul><li>are combined in 52 groups, </li></ul></ul><ul><ul><li>at this level many socio-economic status </li></ul></ul><ul><ul><li>measures are available: </li></ul></ul><ul><ul><ul><li>educational, </li></ul></ul></ul><ul><ul><ul><li>occupational, </li></ul></ul></ul><ul><ul><ul><li>household-based indicators, </li></ul></ul></ul><ul><ul><ul><li>etc. </li></ul></ul></ul>
    11. 11. Exposure assessment (1) <ul><li>First-generation Gaussian-type dispersion model. </li></ul><ul><li>Surface </li></ul><ul><li>topography, </li></ul><ul><li>Wind </li></ul><ul><li>rose, </li></ul><ul><li>MSWI </li></ul><ul><li>characteristics, </li></ul><ul><li>Etc. </li></ul>
    12. 12. Exposure assessment (2) <ul><li>It was not possible to assess past exposure because past dioxin emission rates had not been collected. </li></ul><ul><li>However, dispersion modeling is heavily influenced by factors that are stable over time (mean meteorological conditions, terrain elevations and stack height). </li></ul><ul><li>Thus, we assumed that contour shapes were reliable estimates of past dioxin exposure profiles, provided relative figures rather than absolute figures were used: </li></ul><ul><ul><li>the contours were classified as very low, low, intermediate, and high exposure areas. </li></ul></ul>
    13. 13. Modeled average ground-level dioxin concentrations < 0.0001 pg/m 3 0.0001 - 0.0002 pg/m 3 0.0002 - 0.0004 pg/m 3 0.0004 - 0.0016 pg/m 3 Dioxin concentrations Municipal solid waste incinerator Doubs river City boundary Soil samples 5 km N
    14. 14. Geographical information System <ul><li>The respective contours of these modeled ground-level ground-level air concentrations were digitalized and contoured onto the surface of a map. </li></ul><ul><li>We used residential address geocoding to pinpoint the location of case residence, and block centroid geocoding to pinpoint the location of control residence. </li></ul><ul><li>We overlaid a map of case residences onto the digital dioxin concentration map to obtain a field -for risk- classification for each cancer patient. </li></ul><ul><li>In the same way, we attributed a dioxin concentration category to each of the 705 city blocks and 52 block groups. </li></ul>
    15. 15. Data analysis <ul><li>We used conditional logistic regressions to calculate odds ratios and 95% confidence intervals for each level of dioxin exposure estimated from the dispersion model. </li></ul><ul><li>Multilevel models were run to explain the outcome (case/control status) defined at the individual level, while introducing risk factors at the individual level (dioxin exposure) and the block group level (socio-economic characteristics). </li></ul>
    16. 16. Results
    17. 17. Socio-economic characteristics 30 12 14 35 Single-family houses (%) 2.2 2.2 1.9 2.2 Number of persons per dwelling (mean) 36 29 32 35 Owner-occupied houses (%) 9 11 8 7 Single woman as head of household (%) 13 15 15 13 Unemployed in labor force (%) 23 26 24 17 Workers in labor force (%) 55 48 49 47 Women in labor force (%) 28 27 30 34 Persons with a high school diploma (%) High Intermediate Low Very low
    18. 18. Description of the population <ul><li>During the 16-year study period, 225 NHL cases were diagnosed: </li></ul><ul><ul><li>age-standardized (world) incidence rate: 14.9 per 100,000, </li></ul></ul><ul><ul><li>to be compared to 7.8 per 100,000 for France as a whole. </li></ul></ul><ul><li>The proportion of male was 51 %. </li></ul><ul><li>The media n age was 66 years. </li></ul><ul><li>Address matching was successful for 222 cases. </li></ul>
    19. 19. Association of NHL with dioxin exposure 2.3 (1.4-3.8) 146 31 High 0.9 (0.6-1.4) 681 58 Intermediate 1.0 (0.7-1.5) 952 91 Low 1.0 441 42 Very low OR (95% CI) Controls Cases Dioxin exposure
    20. 20. Hierarchical models <ul><li>Adjustment for a wide range of block group characteristics, introduced in turn in a 2-level hierarchical model, did not alter the results. </li></ul><ul><li>Inclusion of socio-economic measures resulted in ORs ranging: </li></ul><ul><ul><li>from 0.9 to 1.0, for the low exposure category, </li></ul></ul><ul><ul><li>from 0.9 to 1.0, for the intermediate exposure category, </li></ul></ul><ul><ul><li>from 2.1 to 2.4, for the high exposure category. </li></ul></ul>
    21. 21. Discussion
    22. 22. Strengths <ul><li>We used a population-based design. </li></ul><ul><li>This GIS-based case-control study improved upon the conventional case-control design: </li></ul><ul><ul><li>based on a complete directory of city residents (census data), </li></ul></ul><ul><ul><li>with a high control/case ratio (10-to-1), yielding fairly precise relative risk estimates. </li></ul></ul><ul><li>The dioxin exposure was retrospectively assessed from a Gaussian-type dispersion model, independently performed by a sub-contracting company. </li></ul><ul><li>Sensitivity analyses, based on multi-level modeling, were carried out. </li></ul>
    23. 23. Limitations <ul><li>We lacked actual exposure data regarding biota or exposed humans, and the accuracy of the dispersion model had not been assessed before. </li></ul><ul><li>The lack of information pertaining to residence history and time-activity patterns limited our ability to ascertain the duration of exposure. </li></ul><ul><li>The scarcity of covariates (only age and gender) could potentially confound the relationship between dioxin exposure from the MSWI and NHL: </li></ul><ul><ul><li>a further study has validated the geographic-based exposure through dioxin measurements from soil samples, </li></ul></ul><ul><ul><li>a more detailed case-control study, in which dioxins are measured in blood, is currently under way. </li></ul></ul>
    24. 24. Summary
    25. 25. <ul><li>W e find an increased risk of non-Hodgkin lymphoma in the highest exposure zone around a municipal solid waste incinerator that emitted high levels of dioxins. </li></ul><ul><li>This finding, together with the non-Hodgkin lymphoma mortality excess reported by Bertazzi et al . around Seveso, lends support to the hypothesis that airborne dioxin exposure may be a public health concern. </li></ul><ul><ul><li>Floret N, Mauny F, Challier B, Arveux P, Cahn JY, Viel JF. Dioxin emissions from a solid waste incinerator and risk of non-Hodgkin lymphoma. Epidemiology 2003;14:392-398. </li></ul></ul>
    26. 26. Thank you for your attention…